About OMICS Group
OMICS Group International is an amalgamation of Open Access
publications and worldwide international science conferences and events.
Established in the year 2007 with the sole aim of making the information
on Sciences and technology ‘Open Access’, OMICS Group publishes 400
online open access scholarly journals in all aspects of Science,
Engineering, Management and Technology journals. OMICS Group has
been instrumental in taking the knowledge on Science & technology to the
doorsteps of ordinary men and women. Research Scholars, Students,
Libraries, Educational Institutions, Research centers and the industry are
main stakeholders that benefitted greatly from this knowledge
dissemination. OMICS Group also organizes 300 International
conferences annually across the globe, where knowledge transfer takes
place through debates, round table discussions, poster presentations,
workshops, symposia and exhibitions.
About OMICS Group Conferences
OMICS Group International is a pioneer and leading science event
organizer, which publishes around 400 open access journals and
conducts over 300 Medical, Clinical, Engineering, Life Sciences,
Pharma scientific conferences all over the globe annually with the
support of more than 1000 scientific associations and 30,000 editorial
board members and 3.5 million followers to its credit.
OMICS Group has organized 500 conferences, workshops and national
symposiums across the major cities including San Francisco, Las Vegas,
San Antonio, Omaha, Orlando, Raleigh, Santa Clara, Chicago,
Philadelphia, Baltimore, United Kingdom, Valencia, Dubai, Beijing,
Hyderabad, Bengaluru and Mumbai.
Fluorescence Imaging of Cancer by
Molecular Response to COX-2 Enzymes
Jiangli Fan
State Key Laboratory of Fine Chemicals
Dalian University of Technology, China
[email protected]
Cancer : One of the Major Causes of Death World-wide
China’s Population Motality in 2010
Disease Name
Percentage
Ranking
Cancer
27.01%
1
Heart Disease
20.77%
2
Cerebrovascular
Disease
20.36%
3
In 2008 resulted in 7.6 million deaths
(13% of the total)
 Cancer is a major public health problem, although progress has
been made in reducing incidence and mortality rates, it still
causes numerous deaths world-wide
 Early diagnosis of cancer is particularly important for reducing
cancer mortality.
Cancer diagnostic methods
 Magnetic Resonance Imaging (MRI)
 B Ultrasound
 Positron Emission Tomography (PET) imaging
 Computed Tomography (CT)
 X-ray imaging
Each of these methods has its drawbacks,
such as relatively low resolution, narrow time
window, high instrument cost and injection of
radioactive agents. Apart from that, they
are often not effective until the middle and
terminal cancer.
From Fluorescent Dyes to Diseases Diagnosis and Surgery
Lesions have produced in
your body for a long time
when you feel a pain.
Occurrence of diseases is
from mutations of DNA,
RNA and enzymes to
body's pain
Macro
Micro
Fluorescent Dyes & Probes
A few probes for surgery
using DNA, RNA or
enzymes as imaging
targets have been
reported.
For the early diagnosis of cancer due to its highselectivity, high-resolution, and noninvasive capabilities.
GGT targeted probe
 GGT : g-glutamyltranspeptidase, a cell surface–associated (or bound) enzyme
involved in cellular glutathione homeostasis, overexpressed in several human tumors,
including those from cervical and ovarian cancers.
 A small-molecule fluorescent probe for detection of cancer using GGT as target can be
used in not only fluorescence imaging but also endoscopy system (ESS)
Urano Y, et al. Sci. Transl. Med., 2011, 3, 110-119.
hNQO1 targeted probe
 hNQO1 : the cancer-associated human NAD(P)H, quinone oxidoreductase isozyme 1.
 Quenching of molecular probe fluorescence is achieved through unique photoinduced
electron transfer between the naphthalimide dye reporter and a covalently attached,
quinone based enzyme substrate. Fluorescence is turned on by rapid removal of the
quinone quencher highly selectively by HNQO1.
McCarley R. L. et al. J. Am. Chem. Soc., 2013, 135, 309–314.
The different crystal structure in the different concentration
Hydrophobic cavity
> 0.085ug/ml
< 0.085ug/ml
Monomer
Homotype Dimer
COX-2: Cyclooxygenases, absent or expressed at very low levels
in most normal cells but expressed at high levels in inflammatory
lesions and many tumors
Curr Opin Struct Biol 2001, 11,752–760.
Nature 1996, 384,,644–648.
The advantages of two-photon technology
Excellent fluorescence with two-photon features such as
increased penetration depth, localized excitation and prolonged
observation time.
Long linker
Fluorophore
Recognition group
Free ANQ-IMC-6
After combined with
COX-2
a. Fluorescence emission spectra of ANQ-IMC-6 (2.0 μM) in the absence
and presence of COX-2 (0.50 μg/ml) in buffer at 25 oC.
b. Changes in fluorescence with different biomolecules (0.050 μg/ml) in
buffer. 1, control; 2, COX-2; 3, RNA; 4, DNA; 5, triacylglycerol
acylhydrolase; 6, lysozyme; 7, proteinase k; 8, histone; 9, collagen; 10,
hemoglobin; 11, BSA; 12, β-amylase; 13, trypsin; and 14, chymotrypsin.
c. Emission spectra of ANQ-IMC-6 (2.0 μM) upon the addition of COX-2 (01.0 μg/ml.) in buffer.
d. The fluorescence of ANQ-IMC-6 (2.0 μM) related to COX-2 concentration
(0.05–0.72 μg/ml).
The detection limit for COX-2 was determined as 0.11
μg/ml , higher than the minimum expression of COX-2
(0.085 μg/ml) in cancer cells.
The activated two-photon action cross section (Φδ)max of ANQ-IMC-6 is 118 GM
(1GM= 10-50 cm4 s/photon) when excited at 800 nm in the presence of COX-2 (0.50
μg/ml), and there was a 25-fold enhancement in the value (Φδ)max compared with
that seen in the absence of COX-2.
Selectively imaging living cancer cells
cancer cells
normal cells
Incubation time 15 mins：
 Strong and stable fluorescence
in both cancer cells
 Negligible fluorescence in
both normal cells
Fluorescence intensity /a.u.
2400
2000
Hela cell
MCF-7 cell
HEK293T cell
COS-7 cell
1600
Prolong incubation time （6 h）：
1200
· Still obvious fluorescence in cancer cells
800
· Still negligible fluorescence in normal cells
400
0
0
1
2
3
Time /h
4
5
6
Selective 3D depth imaging of living cancer tissues
The sarcoma 180 tissue slices could be clearly visualized by green
fluorescence at 50-550 μm depth . Only negligible fluorescence was
observed in normal liver tissue slices.
Specific localization of Golgi Apparatus of cancer cells.
Fluorescence images of ANQ-IMC-6 (5.0 μM) and BODIPY TR C5-ceramide (5.0
μM) in HeLa cells. a, and b, Stained with ANQ-IMC-6. a, excitation wavelength =
800 nm, scan range = 530-570 nm. b, excitation wavelength = 488 nm, scan range =
530-570 nm. c, Stained with BODIPY TR C5-ceramide, excitation wavelength = 543
nm, scan range = 600-640 nm. d, Merged image of b, and c. e, Intensity correlation
plot of stain ANQ-IMC-6 and BODIPY TR C5-ceramide.
Imaging morphological changes of the Golgi apparatus
during the cancers cells apoptosis.
 Golgi body gradually disintegrated,
to form the apoptotic bodies
 Fluorescent dye can be used to
in situ real-time observe changes
of cancer cells golgi apparatus
Fan JL and Peng XJ, J. Am. Chem. Soc., 2013, 135, 11663-11669.
Summary
 A PET-quenched molecular probe (ANQ-IMC-6), a
fluorogenic derivative of a COX-2 inhibitor was reported,
whose fluorescent signal is selectively and quickly generated
by interaction with COX-2 accumulating in the Golgi
apparatus of cancer cells.
The push-pull charge-transfer structure of ANQ-IMC-6
provides significant two-photon properties permitting the
selective identification of and screening for cancer cells.
We anticipate that ANQ-IMC-6 could serve as a practical
tool for the early diagnosis of cancers.
Acknowledgements
Co-workers:
Professor Xiaojun Peng
Dr. Jingyun Wang
Dr. Jianjun DU
Graduate students:
Dr. Hua Zhang
Benhua Wang
NSFC (Natural Science Foundation of China)
Education Ministry of China
Ministry of Science and Technology of China
Let Us Meet Again
We welcome you all to our future
conferences of OMICS Group
International
Please Visit:
www.omicsgroup.com
www.conferenceseries.com
www.pharmaceuticalconferences.com